TAS-102 and Yttrium-90 Microsphere Radioembolization in Treating Patients with Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

Status: Active

Description

This phase I trial studies the side effect and best dose of trifluridine / tipiracil hydrochloride combination agent TAS-102 (TAS-102) and to see how well it works when given together with Yttrium-90 microsphere radioembolization in treating patients with colorectal cancer that has spread to other places in the body and cannot be removed by surgery. Drugs used in the chemotherapy, such as trifluridine / tipiracil hydrochloride combination agent TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemoembolization kills tumor cells by carrying drugs directly into blood vessels near tumors and then blocking the blood flow to allow a higher concentration of the drug to reach the tumor for a longer period of time. Chemoembolization may cause fewer side effects in treating patients with colorectal cancer. Giving trifluridine / tipiracil hydrochloride combination agent TAS-102 and Yttrium-90 microsphere radioembolization may work better in treating patients with colorectal cancer.

Eligibility Criteria

Inclusion Criteria

  • Of any ethnic or racial group
  • Diagnosis of unresectable metastatic colorectal adenocarcinoma with liver-dominant bilobar disease; diagnosis may be made by histo- or cyto-pathology, or by clinical and imaging criteria as is standard of care at University of California, San Francisco (UCSF)
  • Disease progression or intolerance to at least two prior Food and Drug Administration (FDA)-approved therapeutic regimens
  • If extrahepatic disease is present, it must be asymptomatic
  • If a primary tumor is in place, it must be asymptomatic
  • Measurable target tumors using standard imaging techniques (RECIST version [v.] 1.1 criteria)
  • Tumor replacement =< 50% of total liver volume
  • Current Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 through screening to first treatment on study
  • Completion of prior systemic therapy at least 14 days prior to enrollment
  • Able to understand informed consent

Exclusion Criteria

  • At risk for hepatic or renal failure * Serum creatinine > 1.5 mg/dl * Serum bilirubin > 1.3 mg/ml * Albumin < 2.0 g/dL * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper normal limit * Any history of hepatic encephalopathy * Cirrhosis or portal hypertension * Clinically evident ascites (trace ascites on imaging is acceptable)
  • Contraindications to angiography and selective visceral catheterization * Any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device) * Severe allergy or intolerance to contrast agents, narcotics, or sedatives that cannot be managed medically
  • Symptomatic lung disease
  • Prior therapy with TAS-102
  • Contraindications to TAS-102 * Absolute neutrophil count < 1,500/ul * Platelet count < 75,000/ul * Allergy or intolerance to TAS-102
  • Unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 2 due to prior therapies
  • Evidence of potential delivery of * Greater than 30 Gy absorbed dose of radiation to the lungs during a single 90Y resin microsphere administration; or * Cumulative delivery of radiation to the lungs > 50 Gy over multiple treatments
  • Evidence of any detectable technetium Tc-99m albumin aggregated (Tc99m MAA) flow to the stomach or duodenum, after application of established angiographic techniques to stop such flow
  • Previous radiation therapy to the lungs and/or to the upper abdomen
  • Any prior arterial liver-directed therapy, including transarterial chemoembolization (TACE), arterial embolization (TAE), and 90Y radioembolization
  • Any intervention for, or compromise of the ampulla of Vater
  • Active uncontrolled infection; presence of latent or medication-controlled human immunodeficiency virus (HIV) and/or viral hepatitis is allowed
  • Significant extrahepatic disease * Symptomatic extrahepatic disease (including primary tumor, if unresected) * Greater than 10 pulmonary nodules (each =< 20 mm in diameter) or combined diameter of all pulmonary nodules > 15 cm * Peritoneal carcinomatosis
  • Life expectancy less than 3 months
  • Pregnant or lactating female
  • In the investigator’s judgment, any comorbid disease or condition that would place the patient at undue risk and preclude safe use of radioembolization or TAS-102

Locations & Contacts

California

San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Contact: Nicholas Fidelman
Phone: 415-353-1300
Email: Nicholas.Fidelman@ucsf.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine maximum tolerated dose (MTD) of TAS-102 when used in combination with liver radioembolization using Yttrium-90 (90Y) resin microspheres.

II. To determine dose limiting toxicities of TAS-102 when used in combination with liver radioembolization using 90Y resin microspheres.

III. To determine the safety (adverse events) of TAS-102/90Y radioembolization combination therapy.

SECONDARY OBJECTIVES:

I. To measure radiographic overall response rate (by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) to combination of TAS-102 and radioembolization using 90Y resin microspheres.

II. To measure progression free survival (PFS).

III. To measure hepatic progression free survival (HPFS).

IV. To measure extrahepatic progression free survival (EHPFS).

V. To measure overall survival (OS).

VI. To measure proportion of patients with carcinoembryonic antigen (CEA) response defined as >= 50% decline from baseline (in patients with baseline level >= 3.2) post combination therapy with TAS-102 and 90Y radioembolization.

OUTLINE: This is a dose escalation study of trifluridine/tipiracil hydrochloride combination agent TAS-102.

Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally on days 1, 2, 4, 5, and 8-13 of courses 1 and 2, and then on days 1-5 and 8-12 of subsequent courses. Patients undergo Yttrium-90 microsphere radioembolization on day 3 of courses 1 and 2. Courses repeat every 28 days in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
UCSF Medical Center-Mount Zion

Principal Investigator
Nicholas Fidelman

Trial IDs

Primary ID 16452
Secondary IDs NCI-2017-01321, 16-18798
Clinicaltrials.gov ID NCT02602327